Novel combination of ITGB2 mutations causing leukocyte adhesion deficiency type 1 (LAD-1)

Abstract

In this case report, we describe for the first time the identification of a compound heterozygote mutation in the β2 integrin gene (ITGB2), which is associated with Leukocyte Adhesion Deficiency type 1 (LAD-1). The patient was a 6-year-old male referred for evaluation of multiple recurrent infections. Laboratory evaluation revealed persistent leukocytosis with normal immunoglobulins, complement, mannose-binding lectin, and vaccine antibodies. There was also a complete absence of the integrins – CD18 and CD11a on monocytes, granulocytes and lymphocytes, and CD11b on monocytes and lymphocytes with normal expression on granulocytes. Gene sequencing showed two heterozygous mutations, one being a missense mutation, G284S in exon 7 (c.850G>A), and the second, a single base-pair deletion resulting in a premature stop codon (c.2070delT). Based on the clinical and laboratory findings, a diagnosis of LAD-1 was reached, but it was delayed by an apparent lack of early recognition of the clinical features. LAD-1 should be considered as a potential diagnosis and aggressively pursued in any patient who presents with leukocytosis, delayed umbilical cord separation and non-purulent recurrent infections. Key diagnostic work-up includes flow cytometry for CD18, CD11a and CD11b on white blood cells followed by appropriate confirmatory gene sequencing analysis.

Keywords

Leukocyte adhesion deficiency syndrome - innate immunity - leukocyte adhesion receptors - CD18 integrin - hematopoietic stem cell transplantation